This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The key to understanding the results of the STEP/Phambili trials is first to model the results of the trial in controlled experiments using mucosal SIV inoculation of rhesus macaques. Thus, we will determine the effectiveness and potential of the Merck trivalent HIV adenovirus 5 vector vaccine (V520) for enhancing susceptibility to S1V in a rhesus macaque model of mucosal HIV transmission. If models of vaccine protection or enhancement are established, the immune mechanisms and inflammation/activation associated with any protective or enhancing effects can be defined in a renewal application.